Generation and comparison of 3D dosimetric reference datasets for COMS eye plaque brachytherapy using model-based dose calculations.

PURPOSE: A joint Working Group of the American Association of Physicists in Medicine (AAPM), the European Society for Radiotherapy and Oncology (ESTRO), and the Australasian Brachytherapy Group (ABG) was created to aid in the transition from the AAPM TG-43 dose calculation formalism, the current standard, to model-based dose calculations. This work establishes the first test cases for low-energy photon-emitting brachytherapy using model-based dose calculation algorithms (MBDCAs). ACQUISITION AND VALIDATION METHODS: Five test cases are developed: (1) a single model 6711 125 I brachytherapy seed in water, 13 seeds (2) individually and (3) in combination in water, (4) the full Collaborative Ocular Melanoma Study (COMS) 16 mm eye plaque in water, and (5) the full plaque in a realistic eye phantom. Calculations are done with four Monte Carlo (MC) codes and a research version of a commercial treatment planning system (TPS). For all test cases, local agreement of MC codes was within ∼2.5% and global agreement was ∼2% (4% for test case 5). MC agreement was within expected uncertainties. Local agreement of TPS with MC was within 5% for test case 1 and ∼20% for test cases 4 and 5, and global agreement was within 0.4% for test case 1 and 10% for test cases 4 and 5. DATA FORMAT AND USAGE NOTES: Dose distributions for each set of MC and TPS calculations are available online (https://doi.org/10.52519/00005) along with input files and all other information necessary to repeat the calculations. POTENTIAL APPLICATIONS: These data can be used to support commissioning of MBDCAs for low-energy brachytherapy as recommended by TGs 186 and 221 and AAPM Report 372. This work additionally lays out a sample framework for the development of test cases that can be extended to other applications beyond eye plaque brachytherapy.

Multiscale Monte Carlo simulations of gold nanoparticle dose-enhanced radiotherapy II. Cellular dose enhancement within macroscopic tumor models.

BACKGROUND: Gold NanoParticle (GNP) dose-enhanced radiation therapy (GNPT) requires consideration of physics across macro- to microscopic length scales, however, this presents computational challenges that have limited previous investigations. PURPOSE: To develop and apply multiscale Monte Carlo (MC) simulations to assess variations in nucleus and cytoplasm dose enhancement factors (n,cDEFs) over tumor-scale volumes. METHODS: The intrinsic variation of n,cDEFs (due to fluctuations in local gold concentration and cell/nucleus size variation) are estimated via MC modeling of varied cellular GNP uptake and cell/nucleus sizes. Then, the Heterogeneous MultiScale (HetMS) model is implemented in MC simulations by combining detailed models of populations of cells containing GNPs within simplified macroscopic tissue models to evaluate n,cDEFs. Simulations of tumors with spatially uniform gold concentrations (5, 10, or 20 mgAu /gtissue ) and spatially varying gold concentrations eluted from a point are performed to determine n,cDEFs as a function of distance from the source for 10 to 370 keV photons. All simulations are performed for three different intracellular GNP configurations: GNPs distributed on the surface of the nucleus (perinuclear) and GNPs packed into one or four endosome(s). RESULTS: Intrinsic variations in n,cDEFs can be substantial, for example, if GNP uptake and cell/nucleus radii are varied by 20%, variations of up to 52% in nDEF and 25% in cDEF are observed compared to the nominal values for uniform cell/nucleus size and GNP concentration. In HetMS models of macroscopic tumors, subunity n,cDEFs (i.e., dose decreases) can occur for low energies and high gold concentrations due to attenuation of primary photons through the gold-filled volumes, for example, n,cDEF<1 is observed 3 mm from a 20 keV source for the four endosome configuration. In HetMS simulations of tumors with spatially uniform gold concentrations, n,cDEFs decrease with depth into the tumor as photons are attenuated, with relative differences between GNP models remaining approximately constant with depth in the tumor. Similar initial n,cDEF decreases with radius are seen in the tumors with spatially varying gold concentrations, but the n,cDEFs for all of the GNP configurations converge to a single value for each energy as gold concentration reaches zero. CONCLUSIONS: The HetMS framework has been implemented for multiscale MC simulations of GNPT to compute n,cDEFs over tumor-scale volumes, with results demonstrating that cellular doses are highly sensitive to cell/nucleus size, GNP intracellular distribution, gold concentration, and cell position in tumor. This work demonstrates the importance of proper choice of computational model when simulating GNPT scenarios and the need to account for intrinsic variations in n,cDEFs due to variations in cell/nucleus size and gold concentration.

Multiscale Monte Carlo simulations of gold nanoparticle dose-enhanced radiotherapy I: Cellular dose enhancement in microscopic models.

BACKGROUND: The introduction of Gold NanoParticles (GNPs) in radiotherapy treatments necessitates considerations such as GNP size, location, and quantity, as well as patient geometry and beam quality. Physics considerations span length scales across many orders of magnitude (nanometer-to-centimeter), presenting challenges that often limit the scope of dosimetric studies to either micro- or macroscopic scales. PURPOSE: To investigate GNP dose-enhanced radiation Therapy (GNPT) through Monte Carlo (MC) simulations that bridge micro-to-macroscopic scales. The work is presented in two parts, with Part I (this work) investigating accurate and efficient MC modeling at the single cell level to calculate nucleus and cytoplasm Dose Enhancement Factors (n,cDEFs), considering a broad parameter space including GNP concentration, GNP intracellular distribution, cell size, and incident photon energy. Part II then evaluates cell dose enhancement factors across macroscopic (tumor) length scales. METHODS: Different methods of modeling gold within cells are compared, from a contiguous volume of either pure gold or gold-tissue mixture to discrete GNPs in a hexagonal close-packed lattice. MC simulations with EGSnrc are performed to calculate n,cDEF for a cell with radius r cell = 7.35 $r_{\rm cell}=7.35$  µm and nucleus r nuc = 5 $r_{\rm nuc} = 5$  µm considering 10 to 370 keV incident photons, gold concentrations from 4 to 24 mgAu /gtissue , and three different GNP configurations within the cell: GNPs distributed around the surface of the nucleus (perinuclear) or GNPs packed into one (or four) endosome(s). Select simulations are extended to cells with different cell (and nucleus) sizes: 5 µm (2, 3, and 4 µm), 7.35 µm (4 and 6 µm), and 10 µm (7, 8, and 9 µm). RESULTS: n,cDEFs are sensitive to the method of modeling gold in the cell, with differences of up to 17% observed; the hexagonal lattice of GNPs is chosen (as the most realistic model) for all subsequent simulations. Across cell/nucleus radii, source energies, and gold concentrations, both nDEF and cDEF are highest for GNPs in the perinuclear configuration, compared with GNPs in one (or four) endosome(s). Across all simulations of the (rcell , rnuc ) = (7.35, 5) µm cell, nDEFs and cDEFs range from unity to 6.83 and 3.87, respectively. Including different cell sizes, nDEFs and cDEFs as high as 21.5 and 5.5, respectively, are observed. Both nDEF and cDEF are maximized at photon energies above the K- or L-edges of gold by 10 to 20 keV. CONCLUSIONS: Considering 5000 unique simulation scenarios, this work comprehensively investigates many physics trends on DEFs at the cellular level, including demonstrating that cellular DEFs are sensitive to gold modeling approach, intracellular GNP configuration, cell/nucleus size, gold concentration, and incident source energy. These data should prove especially useful in research as well as treatment planning, allowing one to optimize or estimate DEF using not only GNP uptake, but also account for average tumor cell size, incident photon energy, and intracellular configuration of GNPs. Part II will expand the investigation, taking the Part I cell model and applying it in cm-scale phantoms.